CH13 GI.pptx

POWERPOINTS TO ACCOMPANY Chapter 13 Gastrointestinal Pathophysiology © Springer Publishing Company, LLC. 1 Key Concepts Anatomy One continuous tube from mouth to anus Layered structure Influences: enteric and autonomic nervous systems, hormones and local medi...

POWERPOINTS TO ACCOMPANY Chapter 13 Gastrointestinal Pathophysiology © Springer Publishing Company, LLC. 1 Key Concepts Anatomy One continuous tube from mouth to anus Layered structure Influences: enteric and autonomic nervous systems, hormones and local mediators, immune cells Physiology Characterized by motor activity (motility) Secretions added by glands and organs Segments process all ingested food and drink: mouth—chewing; stomach— pulverizing, mixing; small intestine—mixing for digestion, surface area for absorption; large intestine—water reabsorption and stool formation; rectum and anus—excretion © Springer Publishing Company, LLC. 2 Gastrointestinal Tract Accessory Structures Gastrointestinal (GI) function is closely associated with accessory organs: Salivary glands produce saliva that lubricates food and contains a few enzymes that initiate digestion of starch and fat The liver (covered in Chapter 14, Liver) produces bile that is required for fat digestion The pancreas produces bicarbonate-rich fluid that neutralizes stomach acid and secretes digestive proenzymes that are activated in the small intestine © Springer Publishing Company, LLC. 3  The Layered Structure of the GI Tract Outer serosa Two muscle layers Two nerve plexuses Gland-rich submucosa Inner absorptive © Springer Publishing Company, LLC. 4 region  GI Tract Innervation Enteric nervous system (nerve plexuses) can operate independently to control motility and secretions Parasympathetic innervation from brainstem (vagus nerves) and sacral cord (to pelvic structures) stimulates motility and secretion Sympathetic innervation from thoracic spinal cord is generally inhibitory © Springer Publishing Company, LLC. 5  Hormonal GI Control Hormones secreted by endocrine cells in gut walls allow medium- and long-distance signaling to coordinate activity between segments Examples: G cells in the stomach antrum release gastrin into the blood—gastrin circulates to the parietal cells in the body of the stomach to stimulate gastric acid secretion Cholecystokinin (CCK) secreted by small intestine cells signals presence of fat digestion products—CCK circulates to the gall bladder to stimulate contraction and bile secretion Glucagon-like peptide 1 (GLP-1) secreted from cells in the ileum circulate to the stomach to decrease stomach motility and to the pancreas to promote insulin secretion © Springer Publishing Company, LLC. 6  GI Control by Peptides and Amines The enteric nervous system is rich in opioid peptides and their receptors—a prominent action is to reduce motility, the basis of the use of opioid analogues to treat diarrhea, and of constipation when treating with opioid analgesics Gut enterochromaffin (EC) cells secrete amines: EC cells in the stomach release histamine as a local signal that stimulates gastric acid secretion EC cells in the small intestine secrete serotonin that can increase gastric motility © Springer Publishing Company, LLC. 7  Small Intestine Immune Components The small intestine is richly endowed with immune protections against ingested pathogens Peyer’s patches are hubs of gut immune activity © Springer Publishing Company, LLC. 8  Colon Immune Components The colon contains the majority of the gut microbiota— commensal bacteria that contribute to digestion, immune function, and immune tolerance Lymphocytes and macrophages contribute to immune protection of the colon © Springer Publishing Company, LLC. 9  Structure and dysfunction of the esophagus Tube that receives swallowed bolus from the mouth and conveys it to the stomach: peristaltic motility, mucus is secreted as lubricant Narrows at the pharyngeal-esophageal junction, at the point of crossing of the left main bronchus and aortic arch, and at the lower esophageal sphincter (LES) Disorders of the esophagus: Esophageal obstruction: Stenosis due to chronic inflammation, or achalasia due to failure of LES to relax Esophageal cancer: Adenocarcinoma 2º to GERD and Barrett esophagus; squamous cell more common, can be associated with alcohol consumption and cigarette smoking © Springer Publishing Company, LLC. 10  Dysfunction of the esophagus GERD—common cause of esophagitis LES tone normally prevents acidic stomach contents from reaching the esophagus. Reflux is promoted by disorders that allow LES dilation. Reflux is also promoted by factors that alter the pressure gradient across the LES. These are: increased thoracic pressure (deep breathing) or increased abdominal pressure (lying down, Valsalva maneuver, obesity, pregnancy, straining). © Springer Publishing Company, LLC. 11  Structure and Function of the Stomach Strong, muscular hollow organ with ridged lining that contributes to pulverizing food Secretions come from gastric pits that empty into the lumen Motility consists of powerful contractions that mix food with secretions, while gradually expelling meal contents in small spurts through the pylorus into the duodenum. Secretion of gastric acid by parietal cells drops stomach pH as low as 2, activating the proteolytic enzyme pepsin while also killing ingested bacteria Other stomach secretions include pepsinogen (pepsin precursor), mucus, and the hormone gastrin © Springer Publishing Company, LLC. 12  Gastric Glands and Gastric Pits Multiple cell types are represented Parietal cells secrete hydrochloric acid and intrinsic factor Peptic cells secrete pepsinogen Mucous cells secrete bicarbonate-rich mucus to line and protect the stomach © Springer Publishing Company, LLC. 13  Phases of Gastric Acid Secretion Cephalic phase When thinking about food and when meal begins Vagal acetylcholine release is most active Gastric phase The presence of food in the stomach stimulates gastrin, which directly stimulates acid secretion and also stimulates local histamine secretion, synergistically increasing acid secretion Acidification of the stomach lumen inhibits gastrin-secreting cells Intestinal phase Stimulatory signals decrease, inhibitory signals (including prostaglandins) increase, acid secretion slows © Springer Publishing Company, LLC. 14  Stomach Protection from Gastric Acid Mucous neck cells secrete bicarbonate-rich mucus The mucus layer closely lines the stomach—gastric acid is secreted as “jets” that pierce the mucus layer and remain on the lumen side, away from epithelial cells lining the stomach Prostaglandins are protective They reduce acid secretion They increase mucus secretion They increase mucosal blood flow—sweeping away any acid that leaks through and sending cells and allowing rapid healing of any acid-mediated damage Implication—blocking prostaglandin production with nonsteroidal anti- inflammatory drugs (NSAIDs) increases risk of acid damage © Springer Publishing Company, LLC. 15  Stomach Disorders Peptic Ulcers Most common sites: duodenum and stomach Risk increased by hyperacidity, smoking (reduces gastric mucosal blood flow), reflux of small intestine bile acids or digestive enzymes into stomach, NSAIDs Infection with Helicobacter pylori—colonization promotes recurrent ulceration H. pylori infection and chronic gastric inflammation increase risk of stomach cancer Management of GERD and peptic ulcer disease focuses on reducing acid secretion Histamine H2-blocking drugs Proton pump inhibitors Short term antacids to neutralize acid © Springer Publishing Company, LLC. 16  Stomach Motility and Gastroparesis Normal stomach motility Receptive relaxation to accommodate food Strong contractions to promote mixing and move chyme to duodenum Gastroparesis Reduced motility due to altered neural modulation Diabetic autonomic neuropathy Idiopathic Postsurgical © Springer Publishing Company, LLC. 17 Small Intestine—Structure Facilitates Absorption Crypts and villi increase absorptive area Intestinal epithelial cells (IECs) have microvilli on their apical membranes, further increasing absorptive surface area Tight junctions link cells, preventing ingested toxins and pathogens from entering the circulation © Springer Publishing Company, LLC. 18 Digestion Requires Pancreatic Enzymes Pancreatic cells produce a protease inhibitor that also blocks autodigestion of pancreatic cells Secretion of pancreatic enzymes into the gut assists in the breakdown of dietary proteins, carbohydrates, and lipids Pancreatic fluid is rich in bicarbonate—protects duodenum by neutralizing acidic chyme entering from stomach © Springer Publishing Company, LLC. 19 Clinical Aspects of Acute Pancreatitis Causes of acute pancreatitis: gallstones, alcohol, drug reactions Can proceed to critical illness, systemic inflammatory response syndrome, and multiorgan dysfunction Repeated episodes predispose to chronic pancreatitis © Springer Publishing Company, LLC. 20  Basic Principles of Gut Digestion and Absorption Many nutrients are absorbed in proximal small intestine (duodenum, jejunum) Highly vascularized gut supports capillary uptake of digested nutrients and circulation via portal vein to the liver End products of digestion: Starches—glucose, galactose, fructose Proteins—amino acids Triglycerides—free fatty acids and glycerol Phospholipids—free fatty acids and lysophospholipids Cholesterol esters—cholesterol and free fatty acids © Springer Publishing Company, LLC. 21 Common Mechanisms of Diarrhea Secretory—as with cholera, bacterial exotoxins often provoke secretions that overwhelm gut absorption Malabsorptive—loss of gut surface area, seen in celiac disease with villous atrophy due to immune destruction (also can occur after gut diversion by bariatric surgery) Osmotic—as in lactase deficiency—lactose ingestion results in osmotic pull of lactose remaining in gut Inflammatory—inflammatory bowel disease with loss of gut surface area and persistent inflammation © Springer Publishing Company, LLC. 22 Immune-Based Gut Disorders—Celiac Disease Resident immune protections (lymphocytes, dendritic and other antigen-presenting cells, cytokine milieu) predispose to pathologic immune activation that impairs gut function Celiac disease—in sensitive individuals: 1. Ingestion and partial digestion of gluten produces gliadin peptides 2. Gliadin peptides become antigenic 3. Circulating antibodies to gluten, peptides, and transglutaminase increase 4. Gut local inflammation denudes villi, causing malabsorption and diarrhea © Springer Publishing Company, LLC. 23 Inflammatory Bowel Disease Family history and other prior autoimmune diseases are commonly noted in inflammatory bowel disease (IBD) patients. Two major presentations are Crohn disease and ulcerative colitis. Crohn Disease Relapsing/remitting course of abdominal pain with diarrhea Lesions are transmural and discontinuous, most common in ileum High risk of developing transmural lesions and fistulas, complicating care Ulcerative colitis Large surface areas are affected, but lesions only extend to submucosa Greater blood loss than observed in Crohn disease Managed with immunosuppressive drugs—steroids and cytokine-directed biologics © Springer Publishing Company, LLC. 24 Irritable Bowel Syndrome Clinical presentation: Pain/discomfort accompanied by constipation or diarrhea, but without endoscopic evidence of pathology Pathophysiology poorly understood Hypotheses focus on individual vulnerabilities (genetic and behavioral) combined with neuroendocrine alterations and lifestyle influences (environment) Patient tracking includes identification of triggers, exacerbating and relieving factors © Springer Publishing Company, LLC. 25 Lynch Syndrome Colorectal cancer (CRC) is the fourth most common form of cancer in the United States. About 3% of patients with CRC have Lynch Syndrome. Also known as hereditary nonpolyposis colon cancer****** Autosomal dominant: inheriting one abnormal allele of the DNA mismatch repair gene increases risk of many cancers in addition to CRC—women have greater risk of endometrial and ovarian cancer; both men and women have greater risk of cancers of the stomach, hepatobiliary system, small intestine, renal pelvis, and ureter Screenings are carried out with greater frequency in those with the mutation © Springer Publishing Company, LLC. 26 Pediatric Gastroenteritis Acute gastroenteritis—extremely common, particularly in daycare settings. Dehydration and hypovolemia must be carefully managed Viral gastroenteritis is most common, usually rotavirus (for which there is now a vaccine) and norovirus Bacterial gastroenteritis represents about 10% of cases in the United States. Parasitic gastroenteritis—most commonly due to Giardia or Cryptosporidium © Springer Publishing Company, LLC. 27 Pediatric Esophageal Reflux Infantile gastroesophageal reflux (GER)—very common, presents as painless vomiting of large meal, often resolves between ages 6 and 12 months Infant and pediatric gastroesophageal reflux disease (GERD)—can present within first year and thereafter in childhood—signs and symptoms include pain, recurrent vomiting, dysphagia, and food refusal © Springer Publishing Company, LLC. 28 Other Pediatric Gastrointestinal Disorders Hypertrophic pyloric stenosis —present at birth and diagnosed based on history of repeated vomiting, weight loss, and dehydration—resolves with surgical relief of stenosis Intussusception—also a common cause of infant bowel obstruction, can present as severe and sometimes intermittent pain. If obstruction is severe, surgical resection may be needed. Hirschsprung Disease—failure of enteric neurons to innervate a segment of large intestine, causing lack of motility manifested as failure to defecate shortly after birth —managed with resection of affected bowel segment. © Springer Publishing Company, LLC. 29 Gerontologic Considerations Older adults report gastrointestinal (GI) symptoms at higher rates than younger adults, including indigestion, dysphagia, constipation, GERD Problems with mouth and teeth can add to problems with chewing and swallowing—aspiration becomes more common Anatomically, diverticular disease is more common with aging © Springer Publishing Company, LLC. 30